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BACKGROUND AND OBJECTIVE Global Lung Function Initiative (GLI) 2012 equations were developed to resolve the age-related disparity in interpreting spirometry results. Local validation of the equation is needed, especially in Northeast Asian children. This study evaluated the GLI equation in Korean children. METHODS Spirometry indices (FEV1, FVC, FEV1/FVC, and FEF25%-75%) and clinical information were gathered from three population-based birth cohorts. Predicted GLI reference values and z scores of spirometry results were calculated for 1239 healthy children. The mean, standard deviation of z scores were compared with the expected 0 and 1. Probabilities of falling below the lower limit of normal (LLN) (z score: -1.64) were compared with the expected value 5%. GLI z scores were assessed according to low ( 2) BMI z score groups. RESULTS Mean z scores significantly differed from 0 for FEV1/FVC in males (mean [95% confidence interval]: 0.18 [0.08, 0.27]) and forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) in females (-0.23 [-0.31, -0.15] and -0.26 [-0.36, -0.16], respectively). The standard deviation was larger than 1 for all variables in males and FVC and FEV1/FVC in females. The probability of falling below the LLN was significantly larger than 5% for FEV1 (12.13% [9.64, 14.77]), FVC (15.86% [13.06, 18.81]), and forced expiratory flow at 25%-75% of forced vital capacity (FEF25%-75%) (7.31% [5.29, 9.49]) in males and FVC (11.91% [9.40, 14.60]) in females. FEV1 and FVC z scores increased across low to high body mass index (BMI) groups, and FEV1/FVC decreased from low to high BMI groups. CONCLUSION GLI equations marginally differ from real-world values, which should be considered by pulmonologists in practice or research.

Asthma exacerbation (AE) leads to social and economic costs and long-term adverse outcomes. We aimed to predict exacerbation-prone asthma (EPA) in children.The Korean childhood Asthma Study (KAS) is a prospective nationwide pediatric asthma cohort of children aged 5-15 years followed every 6 months. Patients with AE during the 6 months prior to all three visits, with AE prior to one or two visits, and without AE prior to any visit were defined as having EPA, exacerbation-intermittent asthma (EIA), and exacerbation-resistant asthma (ERA), respectively. Risk factors and prediction models of EPA were explored.Of the 497 patients who completed three visits, 42%, 18%, and 15% had exacerbations prior to visits 1, 2, and 3 and 5%, 47%, and 48% had EPA, EIA, and ERA, respectively. Univariate and multivariable logistic regression revealed forced expiratory volume in 1 s (FEV1) z-score, forced vital capacity (FVC) z-score, white blood cell (WBC) count, and asthma control test (ACT) score as relevant EPA risk factors. The EPA prediction model comprised FVC z-score, WBC count, ACT score, sex, and parental education level (area under the receiver operating characteristic curve [AUROC] 0.841 [95% confidence interval (CI): 0.728-0.954]).With appropriate management, AE decreases over time, but persistent AEs may occur. Apart from asthma control level, baseline lung function and WBC count predicted EPA.

Background: It is challenging to diagnose asthma in preschool children. The asthma predictive index (API) has been used to predict asthma and decide whether to initiate treatment in preschool children.Purpose: This study aimed to investigate the association between questionnaire-based current asthma with API, pulmonary function, airway hyperreactivity (AHR), fractional expiratory nitric oxide (FeNO), and atopic sensitization in preschool children.Methods: We performed a population-based cross-sectional study in 916 preschool children aged 4–6 years. We defined current asthma as the presence of both physician-diagnosed asthma and at least one wheezing episode within the previous 12 months using a modified International Study of Asthma and Allergies in Childhood questionnaire. Clinical and laboratory parameters were compared between groups according to the presence of current asthma.Results: The prevalence of current asthma was 3.9% in the study population. Children with current asthma showed a higher rate of positive bronchodilator response and loose and stringent API scores than children without current asthma. The stringent API was associated with current asthma with 72.2% sensitivity and 82.0% specificity. The diagnostic accuracy of the stringent API for current asthma was 0.771. However, no intergroup differences in spirometry results, methacholine provocation test results, FeNO level, or atopic sensitization rate were observed.Conclusion: The questionnaire-based diagnosis of current asthma is associated with API, but not with spirometry, AHR, FeNO, or atopic sensitization in preschool children.

Although bronchial responsiveness (BR) is usually categorized as normal or hyperresponsive to aid the diagnosis of asthma, it exists on a continuous spectrum, not in a dichotomous manner. We aimed to evaluate the distribution profile of BR in a general population of 7-year-olds.In 2015, 7-year-old Korean children from a nationwide birth cohort study visited regional study hospitals for skin prick test, standard spirometry, and bronchial provocation to establish reference values for the general population. Their BR degrees were categorized into five ordered groups: hyperresponsive BRs were classified into group 1 (provocative concentration (PC) of methacholine causing a 20% fall in forced expiratory volume in 1 second [FEV1], PC20 of4 mg/mL) and group 2 (PC20 of ≥4 mg/mL and16 mg/mL), and nonresponsive BRs were categorized into group 3 (final FEV1 percentage fall after inhaling 16 mg/mL of methacholine [FEV1%fall] of15% and ≤20%), group 4 (FEV1%fall of10% and ≤15%), and group 5 (FEV1%fall of ≤10%).In total, 559 subjects finished all tests reliably. Groups 1 and 2 comprised 10.0% and 15.7% of the total population, respectively. Groups 3, 4, and 5 comprised 14.7%, 18.4%, and 41.1%, respectively. As the group number increased, the proportion of those with recent wheezing and those with indoor allergen sensitization decreased (P for trend = 0.001 and P for trend 0.001, respectively), and the baseline FEV1/FVC increased (P for trend 0.001) CONCLUSION: BR of the 7-year-olds in the general population, while showing a wide distribution across phenotypes, is associated with allergic symptoms, negatively correlated with baseline lung function and positively correlated with indoor allergen sensitization.

Cystic fibrosis (CF), caused by mutations in the cystic fibrosis transmembrane conductance regulator (We included 18 pediatric patients with CF diagnosed using sweat chloride test or genetic analysis for 30 years. HEK293 cells were transfected with wild-typeThe median age at diagnosis was 9.2 years. Eleven patients had growth retardation, and 6 had a respiratory failure at diagnosis. Genetic analysis was used for all patients, while sweat testing was for 8 patients. At diagnosis, the medianCF is extremely rare in Korean children and is caused by different mutations from those commonly observed in Caucasians. Early diagnosis and treatment availability may improve outcomes. CFTR modulators may be effective for Asian patients with rare

Background The effect of diet on allergic rhinitis (AR), its severity in children, and whether it modifies AR depending on genetic susceptibility are unknown. We investigated the association between dietary patterns and AR in school children and the influence of diet on AR according to a genetic risk score (GRS). Methods Totally, 435 7-year-old school children were recruited from the Panel Study on Korean Children. We used dietary patterns (vegetable, sugar, and meat) and dietary inflammatory index (DII) as dietary parameters. AR and its severity were defined by questionnaires about treatment in the previous 12 months and the Allergic Rhinitis and its Impact on Asthma (ARIA) guideline, respectively. A GRS was calculated using 6 single nucleotide polymorphisms for allergic diseases. Results A vegetable diet containing a lot of anti-inflammatory nutrients and higher vitamin D level in blood were negatively correlated, while DII was positively correlated with triglyceride level and triglyceride/HDL cholesterol. Vegetable diet (aOR, 95% CI = 0.73, 0.58-0.94) and DII (1.13, 1.01-1.28) were associated with AR risk. In particular, a high-vegetable diet resulted in a lower risk of mild and persistent AR (aOR, 95% CI = 0.24, 0.10-0.56) while a high DII represented a higher risk (2.33, 1.06-5.10). The protective effect of vegetable diet on AR appeared only among children with a lower GRS (adjusted P = .018). Conclusions A vegetable dietary pattern characterized by high intake of anti-inflammatory nutrients and higher vitamin D level in blood might be associated with a lower risk of mild and persistent AR. This beneficial effect is modified by a genetic factor.

Purpose Asthma is a heterogeneous airway disease occurring in children, and it has various clinical phenotypes. A clear differentiation of the clinical phenotypes can provide better asthma management and prediction of asthma prognosis. Little is currently known about asthma phenotypes in Korean children. This study was designed to identify asthma phenotypes in school-aged Korean children. Methods This study enrolled 674 children with physician-diagnosed asthma from the Korean childhood Asthma Study (KAS) cohort. The physicians verified the relevant histories of asthma and comorbid diseases, as well as airway lability and hyper-responsiveness from the results of pulmonary function tests and bronchial provocation tests. Questionnaires regarding the participants' baseline characteristics, their environment and self-rating of asthma control were collected at the time of enrollment. Laboratory tests were performed to assess allergy and airway inflammation. Children with asthma were classified by hierarchical cluster analysis. Results Of the 674 patients enrolled from the KAS cohort, 447 were included in the cluster analysis. Cluster analysis of these 447 children revealed 4 asthma phenotypes: cluster 1 (n = 216, 48.3%) which was characterized by male-dominant atopic asthma; cluster 2 (n = 79, 17.7%) which was characterized by early-onset atopic asthma with atopic dermatitis; cluster 3 (n = 47, 10.5%) which was characterized by puberty-onset, female-dominant atopic asthma with the low lung function; and cluster 4 (n = 105, 23.5%) which was characterized by early-onset, non-atopic dominant asthma. Conclusions The asthma phenotypes among Korean children can be classified into 4 distinct clusters. Long-term follow-up with these phenotypes will be needed to define their prognosis and response to treatment.

Background: Community–acquired pneumonia (CAP) is one of the leading worldwide causes of childhood morbidity and mortality and its disease burden is affected by age and etiologies with time-dependent changes. We aimed to investigate the annual and seasonal patterns in etiologies of pediatric CAP requiring hospitalization. Methods: We conducted a retrospective study in 30,994 children (0-18 years old) with CAP between 2010 and 2015 at 23 nationwide hospitals in Korea. Mycoplasma pneumoniae (MP) pneumonia was clinically classified into macrolide-sensitive MP, macrolide-less effective MP (MLEP) and macrolide-refractory MP (MRMP) based on fever duration after initiation of macrolide treatment, regardless of the results of in vitro macrolide sensitivity tests. Results: MP and respiratory syncytial virus (RSV) were the two most commonly identified pathogens of CAP. With the two epidemics of MP pneumonia (2011 and 2015), the rates of clinical MLEP and MRMP pneumonia showed increasing trends of 36.36% of the total MP pneumonia. In children less than 2 years of age, RSV (34.01%) was the most common cause of CAP, followed by MP (9.44%), whereas MP was the most common cause of CAP in children 2-18 years of age. Systemic corticosteroid was most commonly administered in MP pneumonia. The rate of hospitalization in intensive care unit was highest for RSV pneumonia, and ventilator care was most commonly needed in cases of adenovirus pneumonia. Conclusions: The present study provides fundamental data for establishment of public health policies to decrease disease burden due to CAP as well as for improvement of pediatric health.

BACKGROUND A US Food and Drug Administration (FDA)-approved drug methacholine chloride (Provocholine®) was recently introduced to Korea where it is now widely used in clinical practice. We aimed to evaluate the prevalence, risk factors and cutoff value of bronchial hyperresponsiveness (BHR) to Provocholine in 7-year-old children. METHODS Six hundred and thirty-three children from the Panel Study on Korean Children who visited 16 regional hospitals were evaluated. Skin prick tests, spirometry and bronchial provocation tests for Provocholine as well as a detailed history and physical examinations were performed. The bronchial provocation test was reliably performed on 559 of these children. RESULTS The prevalence of ever-diagnosed asthma via medical records was 7.7%, and that of current asthma (wheezy episode in the last 12 months + diagnosed asthma by physicians) was 3.2%. The prevalence of BHR to Provocholine was 17.2% and 25.8%, respectively, for a PC20 < 8 and < 16 mg/mL. The risk factors for BHR (PC20 < 16 mg/mL) were atopic dermatitis diagnosis and current dog ownership, whereas those for current asthma were allergy rhinitis diagnosis, a history of bronchiolitis before the age of 3, recent use of analgesics/antipyretics and maternal history of asthma. The BHR prevalence trend showed an increase along with the increased immunoglobulin E (IgE) quartile. The cutoff value of PC20 for the diagnosis of current asthma in children at age 7 was 5.8 mg/mL (sensitivity: 47.1%, specificity: 87.4%). CONCLUSIONS BHR to Provocholine (PC20 < 8 mg/mL) was observed in 17.2% of 7-year-olds children from the general population and the cutoff value of PC20 for the diagnosis of current asthma was 5.8 mg/mL in this age group. The risk factors for BHR and current asthma showed discrepancies suggesting different underlying mechanisms. Bronchial provocation testing with Provocholine will be a useful clinical tool in the future.

Polyhexamethylene guanidine phosphate (PHMG) is an antimicrobial biocide that causes severe lung injury accompanied with inflammation and subsequent fibrosis. Cytokines mediate the inflammatory response, leading to fibrosis in injured tissues. PHMG is known to induce the expression of various cytokines in vitro and in vivo. In the present study, we investigated the involvement of three MAPK subfamilies (JNK, p38 MAPK, and ERK) in PHMG-induced cytokine expression in A549 human lung epithelial cells. Our in vivo and in vitro data indicated that PHMG induced an increase in mRNA expression of IL-6 and TNF-α, and enhanced the phosphorylation of JNK, p38 MAPK, and ERK. Further, we investigated the involvement of MAPKs in PHMG-induced mRNA expression of IL-6 and TNF-α using JNK, p38 MAPK, and ERK inhibitors in A549 cells. Pre-treatment with the JNK inhibitor but not the p38 MAPK or ERK inhibitor, significantly attenuated the PHMG-induced mRNA expression of IL-6 and TNF-α. These results suggest that the activation of JNK is involved at least partially in the induction of IL-6 or TNF-α expression by PHMG in A549 cells.

Background: Respiratory viruses play a significant role in the etiology of acute respiratory infections and exacerbation of chronic respiratory illnesses. This study was conducted to identify the epidemiological and clinical characteristics of children with acute viral lower respiratory infections. Methods: This study investigated 1,168 children diagnosed with acute viral lower respiratory tract infections (RTIs) between January 2012 and December 2014. Specimens of respiratory viruses were collected using a nasopharyngeal swab and analyzed by reverse transcriptase polymerase chain reaction. We retrospectively reviewed the medical records and analyzed the clinical features of children hospitalized for acute lower respiratory infections. Results: Respiratory syncytial virus (RSV), the main cause of infection in children aged

Background Sensitization is associated with the exacerbation, severity, and prognosis of allergic diseases in children OBJECTIVE: We characterized the association between sensitization patterns and allergic diseases. Methods A cohort of 548 children was enrolled from Panel Study of Korean Children (PSKC) study. Skin prick tests (SPTs) for 18 common allergens, blood tests, and methacholine bronchial challenge tests were performed at age 7. The Korean version of International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire was used. Results The sensitization rate on SPTs was 46.4%. Sensitization to indoor allergens showed an association with symptoms of asthma (adjusted odds ratio [aOR], 2.39; 95% confidence intervals [95% CIs], 1.10-5.23), allergic rhinitis (AR, aOR 2.08, 95% CIs 1.42-3.06), and atopic dermatitis (AD, aOR 2.36, 95% CIs 1.24-4.50) in the preceding 12 months. In contrast, sensitization to outdoor allergens was associated with AR diagnosis only (aOR 2.40, 95% CIs 1.30-4.41). The number of sensitized allergens was associated with a lifetime diagnosis and symptoms in the preceding 12 months of AR and asthma, but not with AD or BHR. A higher degree of sensitization to indoor allergens was associated with symptoms in the preceding 12 months of asthma, AR, AD, and that for outdoor allergens was associated with symptoms in the prior 12 months of asthma and AR. Conclusion The sensitization patterns including allergen type, number, and degree of sensitization are helpful for interpreting the association between sensitization and allergic diseases and identifying the pathophysiologies and diverse phenotypes of allergic diseases.

Purpose Childhood asthma has a considerable social impact and economic burden, especially in severe asthma. This study aimed to identify the proportion of childhood asthma severity and to evaluate associated factors for greater asthma severity. Methods This study was performed on 667 children aged 5-15 years with asthma from the nationwide 19 hospitals in the Korean childhood Asthma Study (KAS). Asthma was classified as mild intermittent, mild persistent, and moderate/severe persistent groups according to the National Asthma Education and Prevention Program recommendations. Multinomial logistic regression models were used to identify the associated factors for greater asthma severity. Results Mild persistent asthma was most prevalent (39.0%), followed by mild intermittent (37.6%), moderate persistent (22.8%), and severe persistent asthma (0.6%). Onset later than 6 years of age (adjusted odds ratio [aOR], 1.69 for mild persistent asthma; aOR, 1.92 for moderate/severe persistent asthma) tended to increase asthma severity. Exposure to environmental tobacco smoke (aOR, 1.53 for mild persistent asthma; aOR, 1.85 for moderate/severe persistent asthma), and current dog ownership with sensitization to dog dander (aOR, 5.86 for mild persistent asthma; aOR, 6.90 for moderate/severe persistent asthma) showed increasing trends with greater asthma severity. Lower maternal education levels (aOR, 2.32) and no usage of an air purifier in exposure to high levels of outdoor air pollution (aOR, 1.76) were associated with moderate/severe persistent asthma. Conclusions Modification of identified environmental factors associated with greater asthma severity might help better control childhood asthma, thereby reducing the disease burden due to childhood asthma.

Objective: Various numerical asthma control tools have been developed to distinguish different levels of symptom control. We aimed to examine whether the asthma control test (ACT) is reflective of objective findings such as lung function, fractional exhaled nitric oxide (FeNO) and laboratory data in patients with stable asthma. Methods: We included patients who were enrolled in the Korean Childhood Asthma Study. ACT, spirometry, blood tests and FeNO were performed in patients after stabilization of their asthma. We examined differences among spirometry parameters, blood tests and FeNO according to control status as determined by ACT and investigated for any significant correlations. Results: The study population consisted of 441 subjects. Spirometry showed that forced expiratory volume in one second (FEV1), forced expiratory flow between 25% and 75% of forced vital capacity and FEV1/forced vital capacity were all significantly higher in the controlled asthma group. Likewise, FeNO and percent-change in FEV1 were both significantly lower in the controlled asthma group. In blood tests, the eosinophil fraction was significantly lower in the controlled asthma group while white blood cell count was significantly higher in the controlled asthma group. Lastly, among the various factors analyzed, only provocative concentration of methacholine causing a 20% fall in FEV1 significantly correlated with ACT score. Conclusion: ACT is useful as part of the routine evaluation of asthmatic children and should be used as a complement to existing tools such as spirometry and FeNO measurement.

Background Asthma is a syndrome composed of heterogeneous disease entities. Although it is agreed that proper asthma endo-typing and appropriate type-specific interventions are crucial in the management of asthma, little data are available regarding pediatric asthma. Methods We designed a cluster-based, prospective, observational cohort study of asthmatic children in Korea (Korean childhood Asthma Study [KAS]). A total of 1000 Korean asthmatic children, aged from 5 to 15 years, will be enrolled at the allergy clinics of the 19 regional tertiary hospitals from August 2016 to December 2018. Physicians will verify the relevant histories of asthma and comorbid diseases, as well as airway lability from the results of spirometry and bronchial provocation tests. Questionnaires regarding subjects’ baseline characteristics and their environment, self-rating of asthma control, and laboratory tests for allergy and airway inflammation will be collected at the time of enrollment. Follow-up data regarding asthma control, lung function, and environmental questionnaires will be collected at least every 6 months to assess outcome and exacerbation-related aggravating factors. In a subgroup of subjects, peak expiratory flow rate will be monitored by communication through a mobile application during the overall study period. Cluster analysis of the initial data will be used to classify Korean pediatric asthma patients into several clusters; the exacerbation and progression of asthma will be assessed and compared among these clusters. In a subgroup of patients, big data-based deep learning analysis will be applied to predict asthma exacerbation. Discussion Based on the assumption that asthma is heterogeneous and each subject exhibits a different subset of risk factors for asthma exacerbation, as well as a different disease progression, the KAS aims to identify several asthma clusters and their essential determinants, which are more suitable for Korean asthmatic children. Thereafter we may suggest cluster-specific strategies by focusing on subjects’ personalized aggravating factors during each exacerbation episode and by focusing on disease progression. The KAS will provide a good academic background with respect to each interventional strategy to achieve better asthma control and prognosis.

Background Bronchiectasis is a chronic pulmonary disease characterized by progressive and irreversible bronchial dilatation. The aim of the present study was to investigate the etiologies and clinical features of bronchiectasis in Korean children. Methods We performed a retrospective review of the medical records for children diagnosed with bronchiectasis between 2000 and 2017 at 28 secondary or tertiary hospitals in South Korea. Results A total of 387 cases were enrolled. The mean age at diagnosis was 9.2 ± 5.1 years and 53.5% of the patients were boys. The most common underlying cause of bronchiectasis was preexisting respiratory infection (55.3%), post-infectious bronchiolitis obliterans (14.3%), pulmonary tuberculosis (12.3%), and heart diseases (5.6%). Common initial presenting symptoms included chronic cough (68.0%), recurrent pneumonia (36.4%), fever (31.1%), and dyspnea (19.7%). The most predominantly involved lesions were left lower lobe (53.9%), right lower lobe (47.1%) and right middle lobe (40.2%). No significant difference was observed in the distribution of these involved lesions by etiology. The forced expiratory volume in 1 s (FEV1) levels were lowest in cases with interstitial lung disease-associated bronchiectasis, followed by those with recurrent aspiration and primary immunodeficiency. Conclusions Bronchiectasis should be strongly considered in children with chronic cough and recurrent pneumonia. Long-term follow-up studies on pediatric bronchiectasis are needed to further clarify the prognosis and reduce the disease burden in these patients.

PURPOSE Although anaphylaxis is recognized as an important, life-threatening condition, data are limited regarding its triggers in different age groups. We aimed to identify anaphylaxis triggers by age in Korean children. METHODS We performed a retrospective review of medical records for children diagnosed with anaphylaxis between 2009 and 2013 in 23 secondary or tertiary hospitals in South Korea. RESULTS A total of 991 cases (mean age=5.89±5.24) were reported, with 63.9% involving patients younger than 6 years of age and 66% involving male children. Food was the most common anaphylaxis trigger (74.7%), followed by drugs and radiocontrast media (10.7%), idiopathic factors (9.2%), and exercise (3.6%). The most common food allergen was milk (28.4%), followed by egg white (13.6%), walnut (8.0%), wheat (7.2%), buckwheat (6.5%), and peanut (6.2%). Milk and seafood were the most common anaphylaxis triggers in young and older children, respectively. Drug-triggered anaphylaxis was observed more frequently with increasing age, with antibiotics (34.9%) and nonsteroidal anti-inflammatory drugs (17.9%) being the most common causes. CONCLUSIONS The most common anaphylaxis trigger in Korean children was food. Data on these triggers show that their relative frequency may vary by age.

Summary Purpose Bronchial hyper-responsiveness (BHR) is a key feature of asthma. The degree of BHR in children may be altered by several factors. We evaluated the prevalence of BHR according to age and gender in pediatric and adolescent population and analyzed the associated factors for gender differences. Methods Among the 2,067 subjects, methacholine challenge tests were performed in 1,820 children from one elementary and one middle school in Seoul, Korea. A total of 1,725 subjects between 6 and 14 years old were included in the analysis. The prevalence of BHR, defined as a provocative concentration that induced a 20% reduction of FEV1 (PC20) that was less than 8 mg/ml, was evaluated according to age and gender. Gender differences associated with BHR prevalence at each age were calculated and multiple logistic regression analyses were performed to identify factors associated with BHR by gender. Results The prevalence of BHR (PC20 ≤ 8 mg/ml) for each gender decreased with age (P

Purpose Data are lacking on the association between the allergic rhinitis (AR) phenotype and sensitization to specific allergens or bronchial hyperresponsiveness (BHR) in children. We here investigated risk factors and comorbidities, including sensitization to specific allergens and BHR, for the AR phenotype by AR and its Impact on Asthma (ARIA) classification in a general population-based birth cohort study. Methods We enrolled 606 children aged 7 years from the Panel Study of Korean Children. The AR phenotype was assigned in accordance with the ARIA classification in children. Skin prick tests and Provocholine provocation test were performed. Risk factors and comorbidities for AR phenotypes were then analyzed. Results The prevalence of mild and moderate to severe AR in our study cohort was 37.2% and 8.8%, respectively. Recent use of analgesics or antipyretics and current cat ownership were associated with the risk of mild persistent AR. Sensitizations to Dermatophagoides Pteronyssinus (Der p), Japanese hop and cat were associated with moderate to severe persistent AR. Children with moderate to severe AR had a higher risk of current asthma and BHR compared to mild AR cases (adjusted odds ratio [aOR], 5.26; 95% confidence interval [CI], 1.77-15.62). Moderate to severe AR with allergic sensitization was associated with the highest risk of BHR (aOR, 11.77; 95% CI, 3.40-40.74). Conclusions Moderate to severe-persistent AR is more closely related to respiratory comorbidities and sensitizations than mild AR. Stratifying the AR phenotype by ARIA classification may assist in disease management.

This paper presents a speech enhancement method using non-negative matrix factorization (NMF). In the training phase, each basis matrix of source signal is obtained from a proper database, and these basis matrices are utilized for the source separation. In this case, the performance of speech enhancement relies heavily on the basis matrix. The proposed method for which speech basis matrix is made a high reconstruction error for noise signal shows a better performance than the standard NMF which basis matrix is trained independently. For comparison, we propose another method, and evaluate one of previous method. In the experiment result, the performance is evaluated by perceptual evaluation speech quality and signal to distortion ratio, and the proposed method outperformed the other methods. 논문 15-40-04-02 The Journal of Korean Institute of Communications and Information Sciences '15-04 Vol.40 No.04 http://dx.doi.org/10.7840/kics.2015.40.4.619 619 ※ 이 논문은 2012년도 정부(교육과학기술부)의 재원으로 한국연구재단의 지원을 받아 수행된 연구임(No. 2012R1A2A2A01045874). ※ 이 논문은 2014년도 대검찰청 지원을 받아 수행된 연구임. First Author : Department of Electrical and Computer Engineering and the Institute of New Media and Communications, Seoul National University, kskwon@hi.snu.ac.kr, 학생회원 ° Corresponding Author : Department of Electrical and Computer Engineering and the Institute of New Media and Communications, Seoul National University, nkim@snu.ac.kr, 종신회원 * 서울대학교 전기.정보공학부 및 뉴미디어통신공동연구소, hykim@hi.snu.ac.kr 논문번호:KICS2014-12-478, Received December 4, 2014; Revised March 13, 2015; Accepted April 15, 2015 The Journal of Korean Institute of Communications and Information Sciences '15-04 Vol.40 No.04

PURPOSE Although many previous studies have attempted to identify differences between atopic asthma (AA) and non-atopic asthma (NAA), they have mainly focused on the difference of each variable of lung function and airway inflammation. The aim of this study was to evaluate relationships between lung function, bronchial hyperresponsiveness (BHR), and the exhaled nitric oxide (eNO) levels in children with AA and NAA. METHODS One hundred and thirty six asthmatic children aged 5-15 years and 40 normal controls were recruited. Asthma cases were classified as AA (n=100) or NAA (n=36) from skin prick test results. Lung function, BHR to methacholine and adenosine-5'-monophosphate (AMP), eNO, blood eosinophils, and serum total IgE were measured. RESULTS The AA and NAA cases shared common features including a reduced small airway function and increased BHR to methacholine. However, children with AA showed higher BHR to AMP and eNO levels than those with NAA. When the relationships among these variables in the AA and NAA cases were evaluated, the AA group showed significant relationships between lung function, BHR to AMP or methacholine and eNO levels. However, the children in the NAA group showed an association between small airway function and BHR to methacholine only. CONCLUSIONS These findings suggest that the pathogenesis of NAA may differ from that of AA during childhood in terms of the relationship between lung function, airway inflammation and BHR.

The risk of asthma has been increasing in parallel with use of acetaminophen, which is a potential source of oxidative stress. Toll-like receptor 4 (TLR4) plays a critical role not only in innate immunity, but also in mediating reactive oxygen species induced inflammation. Therefore, we investigated associations between acetaminophen usage and TLR4 polymorphism on asthma and bronchial hyperresponsiveness (BHR). The number of 2,428 elementary school children in Seoul and Jeongeup cities was recruited. Subjects who used acetaminophen with a family history of asthma had an increased risk of both asthma diagnosis ever and current asthma. Individuals with CT+TT genotypes at the TLR4 polymorphism, in combination with acetaminophen usage, also demonstrated an increased risk of asthma diagnosis ever (aOR, 2.08; 95% confidence interval [CI], 1.10-3.92). Family history of asthma and acetaminophen usage were risk factors for BHR. Although TLR4 was not an independent risk factor for BHR, individuals with CT+TT genotypes at the TLR4 polymorphism had an increased risk of BHR when combined with acetaminophen usage (aOR, 1.74; 95% CI, 1.03-2.94). In conclusion, acetaminophen usage may be associated with asthma and BHR in genetically susceptible subjects. This effect may be modified by polymorphism at TLR4. Graphical Abstract

Purpose Measurement of the fractional concentration of exhaled nitric oxide (FeNO) is a quantitative, noninvasive, simple, safe method of assessing airway inflammation. While FeNO measurement has been standardized, reference values for elementary school children are scarce. The aim of this study was to establish reference values for FeNO in children. Methods FeNO was measured in elementary school children at 6-12 years of age in Seoul, Korea, following American Thoracic Society guidelines and using a chemiluminescence analyzer (NIOX Exhaled Nitric Oxide Monitoring System, Aerocrine, Sweden). A total of 1,252 children completed a modified International Study of Asthma and Allergy in Children (ISAAC) questionnaire; FeNO was measured in 1,063 children according to the protocol and in 808 children defined as healthy controls. Results Mean FeNO were 10.32 ppb, 16.58 ppb, and 12.36 ppb in non-atopic, atopic, and all 808 healthy controls, respectively. FeNO was not associated with age and gender. The FeNO reference equations were determined by multiple linear regression analysis, taking into account the variables of age, height, weight, total IgE, eosinophil percent, and bronchial hyper-responsiveness (methacholine PC20). FeNO=0.776+0.003×total IgE+0.340×eosinophil percent; coefficient of determination (R2)=0.084 in the 501 healthy non-atopic controls. FeNO=-18.365+1.536×eosinophil percent, R2=0.183 in the 307 healthy atopic controls; and FeNO=-7.888+0.130×Height+0.004×total IgE+1.233×eosinophil percent, R2=0.209 in the 808 all healthy controls. Eosinophil percent was correlated with FeNO in all healthy controls. FeNO was not associated with BMI. Conclusion This study provides reference values for FeNO that can be used to evaluate airway inflammation in elementary school children. Determinants that could most accurately predict FeNO in healthy school-age children were assessed.

Peanut (PN) and tree nuts (TNs) are common causes of anaphylaxis in Western countries, but no information is available in Korea. To feature clinical characteristics of anaphylaxis caused by PN, TNs, and seeds, a retrospective medical record review was performed in 14 university hospitals in Korea (2009-2013). One hundred and twenty-six cases were identified, with the mean age of 4.9 years. PN, walnut (WN), and pine nut accounted for 32.5%, 41.3%, and 7.1%, respectively. The median values of specific IgE (sIgE) to PN, WN, and pine nut were 10.50, 8.74, and 4.61 kUA /l, respectively. Among 50 cases managed in the emergency department, 52.0% were treated with epinephrine, 66.0% with steroid, 94.0% with antihistamines, 36.0% with oxygen, and 48.0% with bronchodilator. In conclusion, WN, PN, and pine nut were the three most common triggers of anaphylaxis in Korean children, and anaphylaxis could occur at remarkably low levels of sIgE.

Background Although previous studies have investigated the association between atopy phenotypes and allergic diseases, atopy characterizations in association with the development of allergic diseases remain poorly understood. Objective To identify atopy phenotypes in school-age children and to evaluate the association between atopy phenotypes and allergic diseases. Methods We enrolled 616 children with atopy defined as 1 or more positive allergen responses on skin prick tests and 665 children without atopy from the Children's Health and Environmental Research (CHEER) study. All children were followed up for 4 years at 2-year intervals. Atopy phenotypes were classified using latent class analysis. Results Four atopy phenotypes were characterized: later sensitization to indoor allergens (cluster 1); multiple early sensitization (cluster 2); early sensitization to outdoor allergens, especially Alternaria , and later sensitization to indoor allergens, including Aspergillus (cluster 3); and early sensitization to indoor allergens and later sensitization to outdoor allergens (cluster 4). New cases of asthma during follow-up were increased in clusters 2 and 3 (adjusted odds ratio [aOR], 2.76 and 4.25, respectively). The risk of new-onset bronchial hyperresponsiveness was highest in cluster 3 (aOR, 5.03). Clusters 2 and 4 had an increased risk of allergic rhinitis (aOR, 7.21 and 2.37, respectively). Conclusion Identification of atopy phenotypes facilitates prediction of the development of asthma and bronchial hyperresponsiveness in school-age children. Our study suggests prevention of additional sensitization is required to modify the progression of allergic diseases.

Background Treatment guidelines for asthma have been established based on asthma severity; there are limitations in the identification of underlying pathophysiology and prediction of prognosis in heterogeneous phenotypes of asthma. Although the complex interactions between environmental and genetic factors affect the development and progression of asthma, studies on asthma phenotypes considering environmental factors are limited. This study aimed to identify asthma phenotypes using latent class analysis including environmental factors in school-age children. Methods We included 235 children (6–8 years) with parent-reported, physician-diagnosed asthma from the Children’s HEalth and Environmental Research (CHEER) study, which is a 4-year prospective follow-up study with 2-year intervals. At every survey, pulmonary function tests, methacholine challenge tests and blood tests with questionnaire were conducted. Results Four asthma phenotypes were identified. Cluster 1 (22% of children) was characterized by high prevalence of atopy and mild symptoms; subjects in cluster 2 (17%) consisted of less atopy and normal lung function, but intermittent troublesome; cluster 3 (29%) experienced late-onset atopic troublesome asthma with decreased lung function in combination with low socioeconomic status; and cluster 4 was associated with early-onset and less-atopic infrequent asthma. Conclusions Late-onset, high atopy, and low socioeconomic status are associated with troublesome persistent asthma phenotype in school-age children. Environmental factors might be implicated in the clinical heterogeneity of asthma. Asthma phenotypes considering diverse factors might be more helpful in the identification of asthma pathogenesis and its prevention. Electronic supplementary material The online version of this article (doi:10.1186/s12890-017-0387-5) contains supplementary material, which is available to authorized users.

Purpose: It is controversial whether indoor pet exposure is either a risk or protective factor developing sensitization to pet allergens or asthma. Therefore, we investigated whether indoor pet ownership entails a risk for the development of asthma and sensitization in childhood. Methods: The Panel Study of Korean Children (PSKC) is a general-population-based birth cohort study that recruited 2,078 mother-baby dyads in Korea between April and July of 2008. Among 1,577 children who were followed up in 2015, 559 underwent skin prick tests, spirometry and bronchial provocation tests using Provocholine. Having a cat or a dog and the prevalence of asthma were evaluated by using self-reported questionnaires and physicians’ medical records. Results: During infancy, the rate of dog ownership was 4.5% (71 of 1,574) and that of cat ownership was 0.5% (8 of 1,574). Of the subjects, 7.9% (n=109) currently had at least 1 dog and 2.5% (n=34) had at least 1 cat. Pet ownership during infancy was associated with sensitization to cats or dogs (adjusted odds ratio [aOR], 4.24; 95% confidence interval [CI], 1.29-13.98), wheezing within 12 months (aOR, 5.56; 95% CI, 1.65-18.75) and current asthma (wheezing episode in the last 12 months+diagnosed asthma by physi cians) (aOR, 6.36; 95% CI, 1.54-26.28). In contrast, pet ownership during the last 12 months was not associated with sensitization to cats or dogs or current asthma. Conclusion: Indoor pet exposure during infancy can be critical for developing sensitization to cats or dogs and asthma in childhood. Avoidance of pet exposure in early life may reduce sensitization to cats or dogs and development of asthma. (Allergy Asthma Respir Dis 2019;7:99-105)

Purpose: Croup is known to have epidemics in seasonal and biennial trends, and to be strongly associated with epidemics of para influenza virus. However, seasonal and annual epidemics of croup have not been clearly reported in Korea. This study aimed to ex amine the seasonal/annual patterns and etiologies of childhood croup in Korea during a consecutive 6-year period. Methods: Pediatric croup data were collected from 23 centers in Korea from 1 January 2010 to 31 December 2015. Electronic medi cal records, including multiplex reverse transcription polymerase chain reaction (RT-PCR) results, demographics and clinical informa tion were cross-sectionally reviewed and analyzed. Results: Overall, 2,598 childhood croup patients requiring hospitalization were identified during the study period. Among them, a total of 927 who underwent RT-PCR were included in the analysis. Males (61.5%) predominated, and most (63.0%) of them were younger than 2 years of age (median, 19 months; interquartile range, 11-31 months). Peak hospitalization occurred in 2010 and 2012 in even-numbered years, and parainfluenza virus (PIV, 39.7%) was the most common cause of childhood croup requiring hos pitalization, followed by respiratory syncytial virus (14.9%), human rhinovirus (12.5%), Mycoplasma pneumonaie (10.6%), and human coronavirus (7.3%). Conclusion: It is concluded that croup hospitalization has a biennial pattern in even-numbered years. PIV may be the most com mon cause of childhood croup; however, croup epidemics could be attributed to other viruses. (Allergy Asthma Respir Dis 2019;7:78-85)

Summary Background Asthma is a complex genetic disorder that is associated with both genetic and environmental factors. The aim of study was to investigate the combined effect of toll-like receptor 4 (TLR4), cluster of differentiation 14 (CD14), and interleukin-13 (IL-13) polymorphisms and bronchiolitis in the development of childhood asthma. Methods A modified International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire was used to survey 1,341 elementary school children and 919 nursery children in Seoul, Korea. TLR4 (rs1927911), CD14 (rs2569190), and IL-13 (rs20541) polymorphisms were genotyped by the TaqMan assay. Results In elementary school and nursery children, parental history of asthma (adjusted odds ratio [aOR] 2.56 [95% CI 1.16–5.63], aOR 3.60 [95% CI 1.66–7.76], respectively), and past history of bronchiolitis (aOR 3.11 [95% CI 1.84–5.24], aOR 3.94 [95% CI 2.27–6.84], respectively) were independent risk factors for asthma diagnosis. When compared to children with each CC of TLR4 polymorphism or TT of CD14 polymorphism or GG of IL13 polymorphism and no past history of bronchiolitis, children with CT or TT of TLR4 polymorphism and past history of bronchiolitis had 4.23 and 5.34 times higher risk to develop asthma, respectively; children with TT of CD14 polymorphism and past history of bronchiolitis had 3.57 and 7.22 times higher risk for asthma, respectively; children with GA or AA of IL-13 polymorphism and past history of bronchiolitis had 3.21 and 4.13 times higher risk for asthma, respectively. Conclusions Family history of asthma or allergic rhinitis and past history of bronchiolitis could be independent risk factors for the development of childhood asthma. The relationship between asthma and bronchiolitis is modified by the TLR4, CD14, and IL-13 polymorphisms in Korean children. Pediatr Pulmonol. 2015; 50:8–16. © 2013 Wiley Periodicals, Inc.

Purpose Previous studies suggest that the concentration of 25-hydroxyvitamin D [25(OH)D] in cord blood may show an inverse association with respiratory tract infections (RTI) during childhood. The aim of the present study was to examine the influence of 25(OH)D concentrations in cord blood on infant RTI in a Korean birth cohort. Methods The levels of 25(OH)D in cord blood obtained from 525 Korean newborns in the prospective COhort for Childhood Origin of Asthma and allergic diseases were examined. The primary outcome variable of interest was the prevalence of RTI at 6-month follow-up, as diagnosed by pediatricians and pediatric allergy and pulmonology specialists. RTI included acute nasopharyngitis, rhinosinusitis, otitis media, croup, tracheobronchitis, bronchiolitis, and pneumonia. Results The median concentration of 25(OH)D in cord blood was 32.0 nmol/L (interquartile range, 21.4 to 53.2). One hundred and eighty neonates (34.3%) showed 25(OH)D concentrations less than 25.0 nmol/L, 292 (55.6%) showed 25(OH)D concentrations of 25.0-74.9 nmol/L, and 53 (10.1%) showed concentrations of ≥75.0 nmol/L. Adjusting for the season of birth, multivitamin intake during pregnancy, and exposure to passive smoking during pregnancy, 25(OH)D concentrations showed an inverse association with the risk of acquiring acute nasopharyngitis by 6 months of age (P for trend=0.0004). Conclusion The results show that 89.9% of healthy newborns in Korea are born with vitamin D insufficiency or deficiency (55.6% and 34.3%, respectively). Cord blood vitamin D insufficiency or deficiency in healthy neonates is associated with an increased risk of acute nasopharyngitis by 6 months of age. More time spent outdoors and more intensified vitamin D supplementation for pregnant women may be needed to prevent the onset of acute nasopharyngitis in infants.

Bronchial hyperresponsiveness (BHR), one of the key features of asthma, has a diverse natural course in school-aged children, but studies on BHR phenotypes are lacking.To classify BHR phenotypes according to onset age and persistence in children and investigate the characteristics and factors associated with each phenotype in a longitudinal study.This study analyzed 1,305 elementary school children from the Children's Health and Environmental Research (CHEER) study, a 4-year, prospective, follow-up study with 2-year intervals starting at a mean age of 7years. Total serum IgE levels and blood eosinophil counts were measured, and allergy workup, including methacholine challenge tests with the International Study of Asthma and Allergies in Childhood questionnaire, was performed at each survey.The 4 BHR phenotypes were classified as non-BHR (n = 942 [72.2%]), early-onset transient BHR (n = 201 [15.4%]), late-onset BHR (n = 87 [6.7%]), and early-onset persistent BHR (n = 75 [5.7%]). Early-onset persistent BHR is characterized by an increased eosinophil count, total serum IgE level, sensitization rate, decreased lung function, and increased risk of newly diagnosed asthma during follow-up (adjusted odds ratio, 3.89; 95% confidence interval, 1.70-8.88). The 2 early-onset phenotypes were associated with peripheral airway dysfunction. The late-onset BHR phenotype was related to increased risks of allergic rhinitis symptoms at baseline and later sensitization against inhalant allergens.The early-onset persistent BHR phenotype in school-aged children is associated with high atopic burden and increased risk of newly diagnosed asthma, whereas the late-onset BHR phenotype related with later sensitization and allergic rhinitis symptoms. Diverse BHR phenotypes in children have specific characteristics that require targeted follow-ups.

Summary. Background: Asthma is a chronic lower airway inflammatory disease. Nitric oxide is an inflammatory mediator produced endogenously in the airway. Previous studies have demonstrated that the fractional concentration of exhaled nitric oxide (FeNO) is increased in asthma. Objectives: To investigate if FeNO concentrations were correlated with wheezing phenotypes in

Since the risk of developing allergic disease increases in individuals exposed to allergens previously, even during the neonatal period, the immunologic status of a fetus may be important in the subsequent development of allergy. We evaluated the fetal factors to predict atopic dermatitis (AD) at 12 months in 412 infants of a COhort for Childhood Origin of Asthma and Allergic Diseases (COCOA) in the general Korean population. Cord blood mononuclear cells (CBMCs) were stimulated with ovalbumin and phytohemagglutinin and cellular proliferative response and concentrations of interleukin-13 and interferon-γ, were measured. The risk of developing AD was greater in boys than girls (OR 1.97, 95% CI 1.26-3.09), infants delivered by cesarean section than vaginally (OR 1.93, 95% CI 1.14-3.26) and infants with than without parental history of AD (OR 2.34, 95% CI 1.29-4.24). The CBMC proliferative response to phytohemagglutinin stimulation was higher in infants with than without AD (P = 0.048), but no difference was observed in ovalbumin-stimulated cells (P = 0.771). Risk factors for the development of AD at 12 months include male gender, delivery by cesarean section and parental history of AD. Increased CBMC proliferative response to phytohemagglutinin stimulation may predict the development of AD at 12 months.

CHARGE (coloboma, heart defect, atresia choanae, retarded growth and development, genital hypoplasia, and ear anomalies/deafness) syndrome is a rare genetic disorder caused by CHD7 mutation and is related to immunodeficiency. A 6-month-old girl with right lung agenesis, congenital heart defects, and ear anomalies developed repeated and serious respiratory infection for a short period. She was clinically diagnosed with typical CHARGE syndrome with severe combined immunodeficiency (T-, B+, NK-); however, CHD7 mutation was not detected. Disseminated BCG infection did not resolve despite administration of anti-tuberculosis drugs and intravenous immune globulins, and she subsequently died of acute respiratory distress syndrome. Pediatr Pulmonol. 2017;52:E4-E6. © 2016 Wiley Periodicals, Inc.

Background Allergic rhinitis (AR) has a wide range of clinical features and may be accompanied by comorbid allergic diseases. Objective To identify rhinitis phenotypes in school aged children and to predict the prognosis for developing bronchial hyperresponsiveness (BHR) and asthma. Methods This prospective follow-up study involved schoolchildren from the Children's Health and Environment Research cohort with current rhinitis, which was defined based on parental-reported, physician-diagnosed rhinitis and symptoms of rhinitis in the previous 12 months. All participants were followed up at 2 and 4 years later. Rhinitis clusters were identified by latent class analysis that used demographic, clinical, and environmental variables. Results In 512 eligible children (age range, 6–8 years), 4 rhinitis phenotypes were identified: cluster 1 (25% of children) was associated with nonatopy and a low socioeconomic status; cluster 2 (36%) was associated with a high-atopic burden but normal lung function; cluster 3 (22%) was associated with a high-atopic burden and impaired lung function; and cluster 4 (17%) was associated with low atopy and a high socioeconomic status. Cluster 3 was associated with the highest total serum IgE levels and blood eosinophil percentages at enrollment and the highest incidence of new cases of BHR ( P = .04) and asthma symptoms ( P = .005) during follow-up. Conclusion The rhinitis cluster of schoolchildren with atopy and impaired lung function is associated with allergic march. This identification of distinct rhinitis phenotypes in affected children may help to prevent allergic march in children with rhinitis.

25-hydroxyvitamin D (25[OH]D) deficiency and genetic variants at the 17q12-21 locus are independent risk factors for respiratory tract infections (RTIs). We aimed to investigate whether the effect of 25(OH)D at birth and 1 year of age and the polymorphism at the 17q12-21 locus, or interactions between these two factors, increase susceptibility to RTIs in the first year of life.We tested cord-blood (CB) 25(OH)D at birth and 1 year of age and genotypes of a variant at the 17q12-21 locus for associations with RTIs, particularly lower respiratory tract infections (LRTIs), and determined whether there exist interactions between 25(OH)D and 17q12-21 genotypes in a birth cohort of 473 infants.The levels of CB 25(OH)D inversely associate with development of RTIs and LRTIs during the first year of life. There exists an inverse association of 25(OH)D at birth, but not at 1 year, with the risk of acquiring LRTIs in early infancy (adjusted odds ratio [aOR], 2.37; 95% confidence interval [CI]: 1.23-4.60; P = 0.010 and aOR, 0.50; 95%CI: 0.23-1.12; P = 0.094). We have also found a significant interaction between CB 25(OH)D and a variant at the 17q12-21 locus with respect to the development of early LRTIs, such that associations between a variant at the 17q12-21 locus and LRTIs are restricted to infants with low CB 25(OH)D concentrations (P for interaction = 0.013). In addition, when infants with a variant at the 17q12-21 locus had been exposed to chronic 25(OH)D deficiency over the first year, their risk of LRTIs was increased.CB 25(OH)D deficiency during fetal life contribute to the development of LRTIs in genetically susceptible infants. Pediatr Pulmonol. 2016; 51:958-967. © 2016 Wiley Periodicals, Inc.

BackgroundRelationship between recurrent wheeze and airway function and inflammation in preschool children is not fully known.ObjectiveTo investigate the relationship between recurrent wheeze and airway inflammation, lung function, airway hyper-reactivity (AHR) and atopy in preschool children.DesignObservational study, comparing forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and mid-forced expiratory flow (FEF25%–75%), dose–response slope (DRS), exhaled nitric oxide (eNO) and atopic sensitisation between children with recurrent wheeze and those without.SettingPopulation-based, cross-sectional study in Seoul and the Gyeonggi province of Korea conducted as a government-funded programme to perform standardised measurement of the prevalence of allergic diseases, and related factors, in preschool children.Participants900 children aged 4–6 years.Primary and secondary outcome measureseNO, FEV1/FVC, FEF25%–75%, DRS, atopic sensitisation and allergic diseases.MethodsChildren completed the modified International Study of Asthma and Allergies in Childhood questionnaire and underwent eNO assessments, spirometry, methacholine bronchial provocation tests and skin prick tests. Recurrent wheeze was defined as having a lifetime wheeze of more than three episodes, based on the questionnaire. The frequency of hospitalisation and emergency room visits was also obtained by means of the questionnaire. ‘Current’ wheeze was defined as having symptoms or treatments within the past 12 months.ResultsThe prevalence of recurrent wheeze was 13.4%. Children with recurrent wheeze showed a higher prevalence of lifetime or current allergic rhinitis (p=0.01 and p=0.002, respectively) and lifetime atopic dermatitis (p=0.007). Children with recurrent wheeze showed lower FEV1/FVC (p=0.033) and FEF25%–75%(p=0.004), and higher eNO levels (p=0.013) than those without recurrent wheeze. However, the DRS, prevalence of atopic sensitisation and serum IgE levels were not significantly different between the two groups.ConclusionsRecurrent wheeze in preschool children may be associated with airway inflammation and diminished airway function, but not with AHR or atopy.

Bronchial hyper-responsiveness (BHR) is a key feature of asthma. The degree of BHR in children may be altered by several factors. We evaluated the prevalence of BHR according to age and gender in pediatric and adolescent population and analyzed the associated factors for gender differences.Among the 2,067 subjects, methacholine challenge tests were performed in 1,820 children from one elementary and one middle school in Seoul, Korea. A total of 1,725 subjects between 6 and 14 years old were included in the analysis. The prevalence of BHR, defined as a provocative concentration that induced a 20% reduction of FEVThe prevalence of BHR (PCBHR declined with age in the Korean pediatric population. A younger age and reduced lung function were common factors related to BHR in both genders. Additionally, atopy was related to BHR in males, whereas sexual maturation was related to BHR in females. These findings have important clinical implications for evaluating of childhood BHR and asthma related to gender. Pediatr Pulmonol. 2016;51:1040-1047. © 2016 Wiley Periodicals, Inc.